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Arachidonic acid metabolites resulting from the cyclooxygenase (COX), lipoxygenase, and cytochrome P450 oxidase enzymatic pathways play pro- and anti-inflammatory roles in allergic airway inflammation (AAI) and asthma. Expression of COX-2 and soluble epoxide hydrolase (sEH) are elevated in allergic airways and their enzymatic products (e.g., prostaglandins and diols of epoxyeicosatrienoic acids, respectively) have been shown to participate in the pathogenesis of AAI. Here, we evaluated the outcome of inhibiting the COX-2 and sEH enzymatic pathways with a novel dual inhibitor, PTUPB, in A. alternata-induced AAI. Allergen-challenged mice were administered with 10 or 30 mg/kg of PTUPB, celecoxib (selective COX-2 inhibitor), t-TUCB (selective sEH inhibitor) or vehicle daily by gavage and evaluated for various features of AAI. PTUPB and t-TUCB at 30 mg/kg, but not celecoxib, inhibited eosinophilic infiltration and significantly increased levels of anti-inflammatory EETs in the lung tissue of allergen-challenged mice. t-TUCB significantly inhibited allergen-induced IL-4 and IL-13, while a less pronounced reduction was noted with PTUPB and celecoxib. Additionally, t-TUCB markedly inhibited eotaxin-2, an eosinophil-specific chemokine, which was only marginally reduced by PTUPB and remained elevated in celecoxib-treated mice. PTUPB or t-TUCB administration reversed allergen-induced reduction in levels of various lipid mediators in the lungs, with only a minimal effect noted with celecoxib. Despite the anti-inflammatory effects, PTUPB or t-TUCB did not reduce allergen-induced airway hyperresponsiveness (AHR). However, development of structural changes in the allergic airways, such as mucus hypersecretion and smooth muscle hypertrophy, was significantly inhibited by both inhibitors. Celecoxib, on the other hand, inhibited only airway smooth muscle hypertrophy, but not mucus hypersecretion. In conclusion, dual inhibition of COX-2 and sEH offers no additional advantage relative to sEH inhibition alone in attenuating various features associated with A. alternata-induced AAI, while COX-2 inhibition exerts only moderate or no effect on several of these features. Dual sEH/COX-2 inhibition may be useful in treating conditions where eosinophilic inflammation co-exists with pain-associated inflammation.

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The effect of season (S), lamb rearing system (RT) and grain supplementation (GS) on post-partum fertility in Katahdin ewes and growth in Katahdin lambs was evaluated. Katahdin ewes were bred to lamb in fall (n = 36) or spring (n = 56) and at approximately 2.5 months post-partum were randomly assigned to be permanently separated or to continue to suckle their lambs for an additional 3 months. All ewes were joined with rams following treatment to synchronize oestrus. Weaned (W, n = 84) and continuously suckled lambs (CSK, n = 88) were fed forage only (n = 84; hay and pasture for fall- and spring-born lambs respectively) or were supplemented (n = 88; 18% crude protein ration ad libitum) and all weighed biweekly. Ewes rebred in the fall had a shorter ram introduction to lambing interval (p < 0.05), higher prolificacy (p = 0.001) and higher lambing rates (p = 0.02); however, the proportion of ewes lambing was not affected by season. The first service lambing rate was lower in ewes continuously suckling lambs in the spring, but not in the fall breeding season (S × RT, p = 0.03). Lambs that continuously suckled their dams and were supplemented grew quicker and gained more (p < 0.001) than their weaned and unsupplemented counterparts. The effect of CSK on growth rate of lambs was greater in the spring (RT × S; p = 0.05), and the effect of supplementation on growth rate of lambs was greater in the fall (GS × S; p < 0.0001). In conclusion, Katahdin lambs achieved higher weight gains from continuous suckling and grain supplementation. Moreover, Katahdin ewes are capable of early rebreeding post-partum while suckling their lambs, which makes them suited for use in accelerated lambing programmes.